Core Insights - Tenaya Therapeutics has had a strong start to the year and is on track to meet its guidance for the year [2] - The company successfully dosed the high-dose cohort in its 201 lead gene therapy program for the leading genetic cause of hypertrophic cardiomyopathy (HCM) and received DSMB clearance, indicating safety [2] - Tenaya Therapeutics has released data from the largest natural history study for children with a specific mutation related to this severe disease [2] - The company is expected to deliver additional data in the second half of the year, with a narrowed guidance to Q4 [3]

Summary of Tenaya Therapeutics FY Conference Call Company Overview - **Company**: Tenaya Therapeutics (NasdaqGS:TNYA) - **Industry**: Biotechnology, specifically focusing on gene therapy for cardiac diseases Key Points and Arguments Company Performance and Milestones - Tenaya Therapeutics reported a strong start to the year and is on track to meet its guidance for 2025 [4][6] - The company successfully dosed the high-dose cohort for its lead gene therapy program, TN-201, targeting hypertrophic cardiomyopathy (HCM) [4][6] - Data from the largest natural history study for HCM, involving 190 patients, is expected to be released in Q4 2025 [7][27] - The company has been accepted for a late-breaker clinical presentation at the American Heart Association (AHA) conference, which is a significant event for Tenaya [6][27] Regulatory Environment - The CEO emphasized a positive environment at the FDA for gene therapy, particularly for rare diseases, with bipartisan support for innovative medicines [10][11] - The FDA has introduced new pathways for rare diseases, which could benefit Tenaya's programs [11] Safety and Immunosuppression - Recent incidents involving deaths in other gene therapy studies raised concerns about immunosuppressive regimens [13][14] - Tenaya's regimen includes prednisone and sirolimus, which has been deemed appropriate and effective [15] - The company has not experienced any significant safety issues, and the safety profile of its therapies remains favorable [27] Protein Measurement and Efficacy - Accurate measurement of protein expression is critical for assessing the efficacy of gene therapies [18][19] - Tenaya has partnered with experts to improve protein measurement techniques, utilizing mass spectrometry for better accuracy compared to traditional methods [20][21] - The company aims to demonstrate that even modest increases in protein expression can lead to significant clinical benefits [37][38] TN-201 Program Updates - Initial data from the TN-201 program showed that two out of three patients had normalized cardiac troponin I levels, indicating a positive response to treatment [27][28] - The upcoming AHA presentation will provide more detailed data on safety and efficacy, including baseline biopsies for all patients [30][31] TN-401 Program Overview - TN-401 targets arrhythmogenic cardiomyopathy, a severe condition affecting approximately 70,000 patients in the U.S. [45] - The program is designed similarly to TN-201, with a focus on safety and efficacy endpoints [48][49] - Initial phase one data is expected to be shared in Q4 2025, with a focus on arrhythmia metrics as key indicators of treatment impact [50][53] Future Directions - Tenaya plans to continue dosing patients and expanding its natural history study, which is the largest of its kind for PKP2 mutations [59][60] - The company is also exploring international expansion and regulatory pathways for accelerated approval based on protein expression and other biomarkers [40][59] Macro Considerations - The CEO views the rise of biotech innovation in China as a positive development for the industry, emphasizing collaboration over competition [63][64] - Tenaya is leveraging artificial intelligence in its drug discovery processes, particularly in capsid engineering and phenotypic screening [65][66] Other Important Content - The company is focused on maintaining a strong safety profile while advancing its gene therapy programs [27][28] - The CEO highlighted the importance of collaboration and data sharing within the biotech community to enhance patient outcomes [64][66]

Core Insights - Tenaya Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing potentially curative therapies for heart disease [1][3] - The CEO, Faraz Ali, will participate in a fireside chat at the Morgan Stanley 23rd Annual Global Healthcare Conference on September 9, 2025 [1] - The company has a pipeline that includes clinical-stage candidates TN-201 and TN-401, targeting specific genetic heart conditions [3] Company Overview - Tenaya Therapeutics aims to address the underlying causes of heart disease through innovative therapies [3] - The company utilizes integrated capabilities such as target validation and capsid engineering to develop its drug portfolio [3] - Current clinical-stage products include TN-301, a small molecule HDAC6 inhibitor for heart failure, along with several early-stage programs [3]

Core Insights - Tenaya Therapeutics presented interim data from the MyClimb study, the largest noninterventional natural history study of pediatric patients with MYBPC3-associated hypertrophic cardiomyopathy (HCM), at the European Society of Cardiology Congress [1][2][5] Group 1: Study Overview - MyClimb study includes over 200 participants diagnosed with MYBPC3-associated HCM before age 18, with data collected from 27 centers across the U.S., Canada, Spain, and the UK [2][5] - The study aims to characterize the relationship between genotype and cardiac measures over time, initiated in 2021 [5] Group 2: Key Findings - 93% of participants had the nonobstructive form of HCM, which currently lacks approved treatment options [3] - Genetic inheritance patterns revealed distinct risk profiles among participants, with nearly all Homozygous group members dying or requiring heart transplants before age one [3] - Compound Heterozygous participants had a median diagnosis age of 2.9 years, with 63% experiencing heart failure-related hospitalizations [3] - Heterozygous children had a median diagnosis age of 6.5 years, with 27% facing heart failure-related hospitalizations [3] Group 3: Predictive Risk Factors - Left Ventricular Mass Index (LVMI) was identified as a significant predictor of risk, with every 10-unit increase associated with a 10% higher hazard of serious events [3] - Genetic profiles and LVMI may inform risk stratification and intervention strategies for pediatric patients [2][3] Group 4: Gene Therapy Development - TN-201 is a gene therapy designed to deliver a working MYBPC3 gene to heart muscle cells, with initial data from the first three patients presented at a prior meeting [7] - The therapy has received Fast Track, Orphan Drug, and Rare Pediatric Drug Designations from the FDA, indicating its potential significance in treating this condition [7] Group 5: Company Background - Tenaya Therapeutics focuses on developing curative therapies for heart disease, with a pipeline that includes TN-201 for MYBPC3-associated HCM and TN-401 for PKP2-associated arrhythmogenic right ventricular cardiomyopathy [8]

Summary of Tenaya Therapeutics (TNYA) KOL Webcast Event Company Overview - **Company**: Tenaya Therapeutics (TNYA) - **Focus**: Development of curative therapies for genetic cardiomyopathies, specifically through gene therapy approaches targeting underlying causes of heart disease [6][7][8] Key Points Discussed Industry Context - **Gene Therapy for Cardiomyopathies**: Tenaya is positioned as an emerging leader in gene therapy for inherited heart conditions, with a focus on addressing root causes rather than symptoms [6][7] - **Pipeline**: The company has three clinical-stage programs, including two novel gene therapies with near-term data readouts [6][7] Clinical Programs 1. **TN-201**: - Target: Hypertrophic Cardiomyopathy (HCM) due to MyBPC3 gene mutations - Status: Advancing towards pivotal studies with data readout planned for Q4 2025 [7][8][21] - Initial data showed positive tolerability and improvements in cardiac hypertrophy measures [21][22] 2. **TN-401**: - Target: Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) caused by PKP2 gene mutations - Status: Ongoing RIDGE-1 clinical study with initial data readout also planned for Q4 2025 [8][23][29] - Focus on safety and efficacy in reducing arrhythmic events and halting heart failure progression [29] Scientific Methodology - **Protein Measurement**: The company emphasizes the importance of measuring protein expression as a surrogate marker for gene therapy efficacy [10][12][35] - **Biopsy Analysis**: Cardiac biopsies are collected to assess gene therapy success through DNA, RNA, and protein quantification [31][32][35] - **Mass Spectrometry**: Utilized for precise protein quantification, allowing for a detailed view of protein levels in complex tissues like the heart [51][52][80] Challenges and Innovations - **Haploinsufficiency**: The majority of patients have one working gene, complicating the measurement of therapeutic protein levels [10][36] - **Normalization Strategies**: The importance of proper normalization techniques in protein measurement to ensure accurate results [56][63] - **Collaboration with Experts**: Engaging with leading experts in the field to refine methodologies and validate findings [37][38][79] Future Expectations - **Data Readouts**: Anticipated data readouts for both TN-201 and TN-401 in Q4 2025, which will provide insights into the efficacy and safety of the therapies [21][22][29] - **Longitudinal Studies**: Ongoing analysis of patient samples to track changes over time, enhancing the understanding of treatment effects [86] Additional Insights - **Patient-Centric Approach**: The company maintains a strong focus on patient outcomes and quality of life improvements through innovative therapies [6][7] - **Regulatory Considerations**: The potential for accelerated approvals based on protein expression as a surrogate marker for efficacy, supported by recent FDA precedents [10][12] This summary encapsulates the critical aspects of Tenaya Therapeutics' KOL webcast, highlighting the company's innovative approach to gene therapy for cardiomyopathies, the status of its clinical programs, and the methodologies employed to measure therapeutic efficacy.

Pipeline and Programs - Tenaya Therapeutics has 3 clinical-stage programs focused on heart disease[9] - TN-201, a gene therapy for MYBPC3-associated HCM, is in Phase 1b/2 clinical trials with data readouts expected in Q4 2025[10, 12] - TN-401, a gene therapy for PKP2-associated ARVC, is in Phase 1b clinical trials with initial data including safety and biopsy results expected in 2025[10, 94] - TN-301, a small molecule HDAC6 inhibitor for HFpEF, has completed Phase 1 trials and is seeking a partner for further development[10, 99, 104] TN-201 for MYBPC3-associated HCM - MYBPC3-associated HCM affects an estimated 120,000 people in the U S alone[22] - Interim Cohort 1 data for TN-201 showed the therapy was well-tolerated at 3E13 vg/kg dose, with no cardiotoxicities and manageable liver enzyme elevations[17, 40] - All three patients in Cohort 1 improved from NYHA class II/III to NYHA class I, and elevated troponin levels dropped by 60% in two patients into normal ranges[19] - TN-201 DNA in cardiac biopsy surpassed preclinical efficacy threshold and compares favorably to peer, with long-term stability achieved[42] - TN-201 RNA expression increased by as much as 13-fold from week 8 to Week 52[46] TN-401 for PKP2-associated ARVC - PKP2-associated ARVC is estimated to affect over 70,000 people in the U S [75] - Preclinical studies showed that a single 3E13 vg/kg dose of TN-401 in a KO mouse model reversed hallmarks of the disease and extended survival[91] - RIDGE natural history study shows that over 80% of ARVC patients continue to experience high PVC count despite standard of care treatments[87]

Summary of Tenaya Therapeutics (TNYA) FY Conference Call Company Overview - **Company**: Tenaya Therapeutics (TNYA) - **Founded**: 2016 - **Mission**: Focus on therapies for heart disease, including both rare genetic forms and prevalent forms [3][4] Pipeline and Clinical Development - **Clinical Stage Assets**: Three clinical stage assets currently in development [4] - **Gene Therapies**: Focus on gene therapies for genetic causes of cardiomyopathy and a small molecule for HFpEF [4] - **Clinical Sites**: Over 40 clinical sites active in seven countries for patient recruitment [4] Gene Therapy Programs TN-201 for MYBPC3 Positive Hypertrophic Cardiomyopathy - **Target Disease**: Leading genetic cause of hypertrophic cardiomyopathy, affecting approximately 120,000 patients in the US [15] - **Mechanism**: Addresses deficiency of myBPC3 protein, leading to heart thickening and potential heart failure [16][17] - **Natural History Study**: MyCLIMB study with over 220 children enrolled to characterize disease progression [20][21] - **Phase 1b Study**: Completed dosing of high dose cohort; initial results show improvement in heart function [25][27] - **Upcoming Data**: Full cohort data expected in Q4 2025, with focus on safety and efficacy [37] TN-401 for PKP2-Related Arrhythmogenic Right Ventricular Cardiomyopathy - **Target Disease**: Accounts for about 40% of arrhythmogenic right ventricular cardiomyopathy cases, approximately 70,000 patients in the US [44] - **Mechanism**: Aims to add a copy of the human gene to improve desmosome function and reduce arrhythmia burden [46] - **Biopsy Data**: Expected in Q4 2025, focusing on vector copy number, RNA, and protein levels [50][51] Safety and Efficacy - **AAV9 Vector**: Selected for its extensive safety database and effectiveness in cardiac applications [5][6] - **Safety Record**: No significant safety issues reported in ongoing trials; adverse events consistent with other gene therapies [13][14] - **Patient Outcomes**: Initial data shows symptomatic improvement in patients treated with TN-201 [25][27] Small Molecule Program TN-301 - **Status**: Completed first-in-human study with 72 patients; well tolerated with no dose-limiting toxicities [55] - **Future Plans**: Exploring opportunities to advance the program, focusing on HFpEF and potentially severe rare diseases [56] Key Takeaways - **Market Opportunity**: Both TN-201 and TN-401 target large orphan conditions with significant unmet medical needs [44][46] - **Data Releases**: Important data updates expected in Q4 2025 for both gene therapy programs, which could influence future clinical development strategies [37][50]

Clinical Programs & Data - Tenaya Therapeutics has 3 clinical-stage programs focused on heart disease [9] - TN-201 for MYBPC3-associated HCM plans data release including longer-term follow-up for Cohort 1 (3E13 vg/kg) and initial safety and biopsy results for Cohort 2 (6E13 vg/kg) in Q4'25 [15] - TN-401 for PKP2-associated ARVC plans data release will include initial Cohort 1 (3E13 vg/kg) data focused on safety and biopsy results in Q4'25 [16] - Interim Cohort 1 TN-201 data showed improvements in ≥ 1 measures of hypertrophy in two of three patients [17] Disease & Patient Populations - MYBPC3-associated HCM is estimated to affect 120,000 people in the U S alone [22] - Approximately 57% of identified genetic variants underlying familial HCM are MYBPC3 mutations [22] - Over 30% of genetic variants underlying childhood-onset HCM are MYBPC3 mutations [22] - PKP2-associated ARVC is estimated to affect >70,000 people in the U S [75] - In ARVC patients, >15% of heart-related deaths in patients < 35 are due to ARVC [75] - In ARVC patients, 23% of ARVC patients present with sudden cardiac death [75] - In ARVC patients, 40% of ARVC patients carry pathogenic PKP2 mutations [75] Capabilities & Milestones - Tenaya has cGMP AAV manufacturing scale achieved; 1000L clinical supply for TN-201 and TN-401 ready [115]

Core Insights - Tenaya Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing potentially curative therapies for heart disease [1][3] - The company will participate in the Canaccord Genuity 45 Annual Growth Conference on August 12, 2025 [1] Company Overview - Tenaya's mission is to discover, develop, and deliver therapies that target the underlying causes of heart disease [3] - The company's pipeline includes clinical-stage candidates TN-201 for MYBPC3-associated hypertrophic cardiomyopathy and TN-401 for PKP2-associated arrhythmogenic right ventricular cardiomyopathy [3] - Tenaya employs integrated capabilities such as target validation, capsid engineering, and manufacturing to create novel medicines based on genetic insights [3] - Additional products in development include TN-301, a small molecule HDAC6 inhibitor for heart failure, and various early-stage programs targeting rare genetic disorders and common heart conditions [3]

Core Viewpoint - Tenaya Therapeutics reported a narrower net loss in Q2 2025 compared to analyst expectations and the previous year, highlighting progress in clinical programs and cost management [1][2]. Financial Performance - The company posted a GAAP net loss per share of $(0.14) for Q2 2025, an improvement of 58.8% from $(0.34) in Q2 2024 [2]. - Total net loss for the quarter was $23.3 million, down 20.8% from $29.4 million in the same quarter last year [2][5]. - Research and Development expenses decreased by 23.0% to $17.4 million from $22.6 million in Q2 2024 [2]. - General and Administrative expenses fell to $6.7 million, down 18.3% from $8.2 million in Q2 2024 [2][5]. - The company ended the quarter with $71.7 million in cash and equivalents, an increase from $61.4 million at the end of 2024 [6]. Business Overview - Tenaya Therapeutics focuses on developing gene therapies for life-threatening heart diseases caused by genetic mutations, specifically targeting hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy [3]. - The company utilizes adeno-associated virus (AAV) vectors to deliver corrective DNA to affected heart cells [3]. Clinical Developments - TN-201 completed enrollment for its first two cohorts in the MyPEAK-1 Phase 1b/2 trial, with positive interim results showing improvement in heart function [7]. - TN-401 completed the first patient cohort in its RIDGE-1 Phase 1b trial and began dosing a second cohort at a higher gene vector dose, with early safety results leading to dose escalation approval [8]. - Both therapies have received FDA orphan drug and Fast Track designations, facilitating their development [10]. Strategic Focus - The company aims to advance its gene therapy programs while managing costs and enhancing its intellectual property and manufacturing capabilities [4]. - Tenaya is committed to independent pipeline progress and has not announced new business development or partnership deals [12]. Outlook - The company projects that its current cash reserves will support operations into the second half of 2026, providing a runway before needing additional financing [14].